Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization.

Long non-coding RNAs (lnc RNAs) are thought to have various functions other than RNA silencing. We tried to evaluate the expression of lnc RNAs in patients with systemic sclerosis ( SSc) and determined whether lnc RNAs controls collagen expression in dermal fibroblasts. lnc RNA expression was determined by real-time PCR and in situ hybridization. Protein and mRNA levels of collagen were analysed using immunoblotting and real-time PCR. We found TSIX, one of the lnc RNAs, was overexpressed in SSc dermal fibroblasts both in vivo and in vitro, which was inhibited by the transfection of transforming growth factor ( TGF)-β1 si RNA. TSIX si RNA reduced the mRNA expression of type I collagen in normal and SSc dermal fibroblasts, but not the levels of major disease-related cytokines. In addition, TSIX si RNA significantly reduced type I collagen mRNA stability, but not protein half-lives. Furthermore, we first investigated serum lnc RNA levels in patients with SSc, and serum TSIX levels were significantly increased in SSc patients. TSIX is a new regulator of collagen expression which stabilizes the collagen mRNA. The upregulation of TSIX seen in SSc fibroblasts may result from activated endogenous TGF-β signalling and may play a role in the constitutive upregulation of collagen in these cells. Further studies on the regulatory mechanism of tissue fibrosis by lnc RNAs in SSc skin lead to a better understanding of the pathogenesis, new diagnostic methods by their serum levels and new therapeutic approaches using siRNAs. [ABSTRACT FROM AUTHOR]